Project highlights

  • Mechanisms by which organisms rapidly respond to sudden environmental changes
  • Mother senses environmental stress signals to produce stress-resistant progeny
  • Use of the most recent genome-editing tools, as well as biochemistry, and next-gen sequencing1

Overview

Sudden environmental changes are challenging for the survival of many organisms. Some organisms evolved mechanisms to cope with uncertainty, by sensing the environment and transmitting selected adaptive traits to the next generation.

We use the nematode Auanema freiburgensis as model to study the mechanisms by which environmental signals sensed by the mother results in the modification of the germline to produce stress-resistant progeny. In this nematode, chemicals produced by nematodes of the same species are used as signals for overcrowding. Thus, by sensing these chemicals, the mother ‘prepares’ the progeny to withstand the lack of food that occurs in overcrowded conditions. The progeny arrests development in the form of larvae, and can survive in the absence of food for several months. Once in a benign environment, the larvae resume development to become self-fertilizing adults.  The main objectives of the project are to identify the chemical nature sensed by the mothers, how the sensory neurons convey the information to the gonad, and how the germline changes result in different kinds of progeny.

Host

University of Warwick

Theme

  • Organisms and Ecosystems

Supervisors

Project investigator

  •  Andre Pires da Silva (University of Warwick)

 

Co-investigators

  • Robin Allaby (University of Warwick)

How to apply

Methodology

Chemicals will be isolated from nematode cultures and tested for their influence on the sex determination and stress-resistance in the F1 generation. To identify the neuron sensing the chemicals, single cells will be tested by killing them with the use of a laser microbeam. The nature of the communication signal between the neuron and the germline will be tested by performing gene knockouts using the genome editing technology. Changes in the germline upon neuronal signal will be tested using immunoprecipitation with antibodies recognizing histone modification markers.

Training and skills

Students will learn to use the latest genome editing technologies (CRISPR-Cas9) to inactivate gene function and to tag genes to visualize their time and site of expression. Furthermore, students will acquire skills in bioinformatics (learn how to code in Unix and R), how to ablate single cells and immunocytochemistry. In addition, students will learn how to organize and execute their experiments in a timely fashion, how to document experiments, prepare presentations, write professional articles and work in a team. Many of those skills are transferable to other disciplines and professions.

Partners and collaboration

The chemical characterization of the signals produced by nematodes will be in collaboration with the chemist Frank C. Schroeder at Cornel University (USA). The characterization of gene expression changes will be performed with the collaboration with the laboratory of Oded Rechavi at Tel-Aviv University (Israel).

Further details

Andre Pires da Silva

University of Warwick

Email: andre.pires@warwick.ac.uk

Please visit the University of Warwick website for application guidance: https://warwick.ac.uk/fac/sci/lifesci/study/pgr/studentships/nerccenta/

Possible timeline

Year 1

Fraction and test chemicals produced by the nematode. Make laser ablations of single neurons.

Year 2

Generate mutants for neuroamines and neuropeptides using CRISPR/Cas9. Characterize mutants. Start immunocoprecipitation experiments.

Year 3

Transcriptome analysis of animals exposed to defined chemicals. Characterise candidate genes involved in cross-generational inheritance using genome editing technologies.

Further reading

  1. Pembrey, M.E., Bygren, L.O., Kaati, G., Edvinsson, S., Northstone, K., Sjostrom, M., Golding, J., and Team, A.S. (2006). Sex-specific, male-line transgenerational responses in humans. Eur J Hum Genet 14, 159-166.
  2. Grossniklaus, U., Kelly, W.G., Ferguson-Smith, A.C., Pembrey, M., and Lindquist, S. (2013). Transgenerational epigenetic inheritance: how important is it? Nat Rev Genet 14, 228-235.
  3. Cossetti, C., Lugini, L., Astrologo, L., Saggio, I., Fais, S., and Spadafora, C. (2014). Soma-to-germline transmission of RNA in mice xenografted with human tumour cells: possible transport by exosomes. PLoS One 9, e101629.
  4. Dias, B.G., and Ressler, K.J. (2014). Parental olfactory experience influences behavior and neural structure in subsequent generations. Nat Neurosci 17, 89-96.
  5. Kaati, G., Bygren, L.O., and Edvinsson, S. (2002). Cardiovascular and diabetes mortality determined by nutrition during parents’ and grandparents’ slow growth period. Eur J Hum Genet 10, 682-688.
  6. Sharma, A. (2015). Transgenerational epigenetic inheritance: resolving uncertainty and evolving biology. Biomol Concepts 6, 87-103.
  7. Devanapally, S., Ravikumar, S., and Jose, A.M. (2015). Double-stranded RNA made in C. elegans neurons can enter the germline and cause transgenerational gene silencing. PNAS 112, 2133-2138.
  8. Heard, E., and Martienssen, R.A. (2014). Transgenerational epigenetic inheritance: myths and mechanisms. Cell 157, 95-109.
  9. Rechavi, O., Houri-Ze’evi, L., Anava, S., Goh, W.S., Kerk, S.Y., Hannon, G.J., and Hobert, O. (2014). Starvation-induced transgenerational inheritance of small RNAs in C. elegans. Cell 158, 277-287.
  10. Rechavi, O., Minevich, G., and Hobert, O. (2011). Transgenerational inheritance of an acquired small RNA-based antiviral response in C. elegans. Cell 147, 1248-1256.
  11. Greer, E.L., Beese-Sims, S.E., Brookes, E., Spadafora, R., Zhu, Y., Rothbart, S.B., Aristizabal-Corrales, D., Chen, S., Badeaux, A.I., Jin, Q., et al. (2014). A histone methylation network regulates transgenerational epigenetic memory in C. elegans. Cell Rep 7, 113-126.
  12. Edison, A.S. (2009). Caenorhabditis elegans pheromones regulate multiple complex behaviors. Curr Opin Neurobiol 19, 378-388.

COVID-19

The student will generate RNAseq data as soon as the project starts. These data can be analysed without having to be in the laboratory. If those data cannot be generated because of laboratory restrictions, the project will shift to the characterisation of the genome of Auanema freiburgensis, for which the sequence has been already generated.